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China & Egypt Using AntiBody Plasma Treatment to Cure Bird Flu Cases

March 10th, 2009, 11:42 PM

Further evidence that Peng's mother likely to have died from bird flu. Also, treatment plan that saved Peng mentioned.

2009-03-10

<founder-content> </founder-content>Highly pathogenic avian influenza this person's word is a mouthful, for just in the area of separation birthday Spend three small PENG (a pseudonym) is obviously too high, so even though she almost died.

From admission to the critically ill and then recovered, and hundreds of man-made travel PENG busy. 21 days, across both the old and the new Lunar New Year, but also across the life and death and beyond something.

Observation period is still

Since cold temperature, in Shanxi Province by the end of February is still cold.

Shanxi Xiaoyi City Indus Village before the town is home PENG's Grandpa.

Su Fang, director of the village health clinic every day to do door-to-door check for PENG, Xiaoyi City People's Hospital's experts also regularly follow-up to the village.

Discharged February 3, the PENG good body no longer has a fever cold. A few days ago, Grandpa and Grandma go to the city with PENG two chest X-ray film, the situation is normal.

PENG has at least six months observation period, every month, wanted to go to Taiyuan Fourth People's Hospital, a review by local doctors and nurses Xiaoyi special vehicles, the journey around 2 hours.

Observation period was not strict requirements, and hospitalization ago, PENG life has been little change. PENG worried because playing much running will cough, originally strapped teeth Grandpa and grandma one, spent more than 800 yuan bought a electric toy car. PENG but only occasionally to play a while, more often and Sisters is still rough, happy when sisters hold each giggle. Only in the face of a stranger when, PENG will shrink to Grandpa behind, carefully looking at each other.

Master of avian flu infection, PENG also under the age of three, is the person currently known avian flu patients, the youngest one. At the same time, she is also infected early eight patients, one of the earliest rehabilitation. The remaining seven patients, only 2 people eventually recovered.

PENG does not know these, it would not care about. She was concerned that when the mother returned with her, when Hunan PLAYING again.

Years ago, the pro tour in Hunan Province, to her and her family brought about by the disaster, are the three-year-old girl in any case can not be clearly known and understood.

Suspected bird flu

。

End of last year, PENG Yan-Mei He Weifang mother with two daughters went to Changsha, to visit his father at home job. except to accompany his mother went to market, and to do business aunt live rice, PENG how little out of the house, which was not quite satisfied with her.

New Year's Day after his grandma and Grandpa suddenly came to Changsha, PENG put back to Shanxi.

This is because HE Wei Mei (mother of Peng -Fla1) suddenly fell ill was admitted to hospital where he died a week after the announcement, the hospital's diagnosis was "severe pneumonia with acute respiratory distress syndrome."

To make matters worse, PENG also begin fever. Back in Shanxi, the disease more and more serious, Grandpa He Hangen cloud that a child is just beginning on the road with tired, and can be PENG situation does not improve. Several urban areas in the village and hospital treatment is not effective after January 14, HE Han-yun and his wife to hurry with the granddaughter of the provincial capital Taiyuan.

6:00 that evening, PENG was admitted to Children's Hospital of Shanxi Province. The chief physician on duty KANG Yu Zhang recalled that at the time the immediate girls pale gray hair, lips purple, and dull eyes, breathing shallow and promote, and even have no response to an acupuncture treatment.

KANG Yu Zhang hastily asked 25-year executive director of the Medical Hao-ping. From the chest, the lung inflammation PENG extremely serious: white shadows of the lungs accounted for two-thirds of the total area, nearly half of the loss of respiratory function.

Grandpa talk He Hangen cloud at the side of the family misfortune. When it comes to the child's mother a week ago of pneumonia at the time of the death of Hunan, vocational-sensitive so that the two doctors called to the elderly.

“

"The child and her mother come into contact with live birds吗?"

"Come into contact with, PENG's aunt on the sale of chickens and ducks in the live poultry market."

People highly pathogenic avian influenza? KANG Yu Zhang said that when she and to look for a long time, chilling.

Check-SARS wards

Easy to discuss a bit, two doctors immediately reported to the Medical Service hospital immediately PENG quarantine measures taken, to the pediatric emergency center 100,000 to clean up the air pressure isolation wards, on the full range of emergency care equipment.

Ex post facto analysis of the Ministry of Health experts believe that the reason why PENG can receive timely treatment and rehabilitation, first of all, thanks to early detection, from admission to isolation was found to less than two hours.

Children's Hospital, director of leadership and the department have been recruited through the night to discuss the emergency hospital, diagnosed as pneumonia of unknown causes, that is people-specific SARS and bird flu, people are one of a high degree of suspicion of avian influenza. This conclusion promptly report to the Shanxi Provincial Health Department Emergency Response Office.

Early the next morning, all the best medical experts in Taiyuan has been organized for a second consultation PENG. After a comprehensive analysis, the Group believes that children with symptoms of pneumonia of unknown causes in line with the standards, the network agreed to direct the Ministry of Health reported.

January 15 afternoon, Shanxi Province Health Department of Health announced the launch emergency plan to respond to two. That night, PENG blood, it kind of secretion samples and related directly to Beijing.

Ministry of Health dispatched two experts - Beijing Children's Hospital Professor Qian Suyun, First Hospital, Peking University Professor Wang Guangfa emergency "airborne" Taiyuan, meanwhilebrought 100 milliliters Kexing Chinese companies and disease control of R & D-specific antibodies in plasma,In addition, the antiviral drug Tamiflu have effects.Later, the results proved that the plasma in the treatment process has played a good role.

According to the deployment of Health Department of Shanxi Province, Taiyuan PENG was emergency transferred to the Fourth People's Hospital emergency ward. This has more than 70 beds are in the building board room during the SARS emergency built, known as the "Shanxi Xiaotangshan." When the last SARS patient discharged from hospital cured, it no longer stationed in sick, in addition to regular disinfection, perennial locking gate.

6 years after the SARS isolation wards have been re-enabled.

Injection of "Wahaha"

Children's Hospital of Shanxi Province, Liu Ke, deputy director of respiratory led war, and the Ministry of Health, Taiyuan four hospital peer together to form, including first aid, respiratory, radiology, paediatrics, nursing, etc. 15 person team of experts.

However, including the Ministry of Health experts, no one met the exceptional cases of avian flu. Liu Ke-war was described as "feeling the stones across the river", "treading on thin ice", each time to fine-tune treatment program, must go through the Group of Experts argued repeatedly to take effect, then a lot of decisions are made at great risk of .
Think because of being easy to use at the problem, broad-spectrum antibiotic was the first suspension. Soon, in the use of hormones on the Group of Experts had heated discussions. Diagnosis and treatment of atypical pneumonia in the previous on domestic hormone had been caused by improper use of sick "femoral head necrosis" and other sequelae. PENG, taking into account only 3 years old, hormone dosage was gradually have consciously stopped.

Liu Ke-war said that the treatment of another key point, the patients are the implementation of the "moderate" respiratory support, that is, from top to bottom in the control of oxygen for the effort, it is necessary to meet the physical needs, but also to eliminate the use of breathing machine to the patients hazards.

Treatment of early, PENG has refused to eat, the Group will move to the book read literacy PENG him, "What to eat? Ice cream? Milk? Wahaha?" When the reference to "Wahaha" when there is feebly PENG locations of the nod. The next two days, using injection needles collected PENG Wahaha calcium milk became the main diet, appetite stimulation, through a child's desire to survive.

The Group believes that nutrition support can be provided for the treatment of much help to restore digestive function the first time, be able to quickly put nutrition to keep up with the years, in fact, any transfusion are the recovery of gastrointestinal function can not be replaced on the body to help.

To pay
At the same time, Taiyuan, Luliang city activated the human avian influenza contingency monitoring, reporting and implementation of epidemicd ay. 67 close contacts have also been isolated, beginning a sustained 15-day medical observation. HE Han-yun on one side of the isolation wards, totally do not know the world outside. In order to meet granddaughter, burning several attempts from jumping through the window of the elderly, health care workers were finally persuaded under.

January 20, held at the Ministry of Health Human bird flu prevention and control work on television and telephone conference, Health Minister Chen Zhu, in particular regard to the Shanxi told: at all costs for medical treatment in children, children with treatment successful, will the National Human bird flu prevention and control work has great significance.

Price quickly emerged - PENG admitted at the news, Children's Hospital of Shanxi Province and Taiyuan Fourth People's Hospital Outpatient Visits rapid decline, and even less than one-third of the same period last year.

S

hanxi Province Health Department director of high Guoshun commented that this is the price, are to pay.

Eventually recovered and were discharged

3 days later, after a group of experts carefully rescue, PENG start of the vital signs gradually stabilized.

。

Experts in private joke, saying that it remanded back to betting yes.
PENG state of getting better. A few days, she has been accustomed to watch the wearing think can only see the eyes of the people begin to see father mother exclaimed.

Liu Ke Zhan and his colleagues take turns waiting, and the development of early psychological intervention plan, to accompany PENG play chat, and enhance her sense of identity. Later, PENG direct isolation wards where male doctors called the "father", female doctors and nurses called "Mother."

However, the risk may occur at any time. LUO Hong-rounds in a Doctor inquiry, PENG suddenly cough up, droplets of the LUO Hong-splashed face. First time wards silence, all terrified, hastened to allow Tamiflu dose LUO Hong prevention.

Then a few days, even if the cessation of oxygen PENG can and "mother" are playing, no longer coughing, lungs mutant images show obvious absorption, increasing the normal indicators of the signs.

Ministry of Health experts early withdrawal.

Chinese New Year's Eve evening, the night shifts round the head nurse does not remain in the hospital accompanied Lei PENG Chinese New Year.

PENG three are the first two days the first month birthday, where all those involved in health care workers have to get together for PENG bought a variety of toys and gifts at ward installed colorful lanterns, the hospital also bought specially give PENG birthday cake.

Zhang Lei, a smile recalled that PENG only eyes before looking at the "father", "mother" who playfully asked: "Why do not you mouth? how you?" Comparison of PENG Gang admitted to hospital at the time of appearance, Zhang Lei said that she felt very happy.

February 3, at 21 days after admission, in accordance with the criteria established by the Ministry of Health, PENG was declared recovered and been discharged. Guoshun high up in the farewell ceremony, said the rehabilitation of PENG that people bird flu is preventable and governance.

Has been hiding in the corridor of Zhang Lei is very sad, because after take off small PENG actually did not recognize her, not her mind. Until she gently shouted the name PENG, PENG only excitedly shouted "Zhang mother," quickly came running Zhang Lei's bosom.

The adviser to the Ministry of Health Alagianflonza bird success in treating a large number of infected cases in a hospital with the Tamiflu drug called Egyptian Aalasr quickly informing parents about the situation and stated the truth about the birds in the house and their vulnerability to death.

Said Dr. Nasserqlqilp diseases consultant, children in the program Good Morning Egypt Egyptian television Sunday that he used over the treatment of additional [Tamiflu] If adopted by the World Health Organization to add the antibody called IGG plasma drawn from more than twenty thousand blood donor

He appealed to Nasser Qalqulya continue to volunteer to donate blood to extract antibodies from the plasma in question succeeded in the treatment of a total of 27 children infected children, 29

He Qlqilp that the bird flu virus usually causes the destruction of nuclei in cells of the vesicles in the air, causing the destruction of the lung respiratory unfortunate theory to resist this anti Altdmiobalajdzam IGG, which proved irresistible to a number of viruses previously designated doctors prevent storm unleashed by the immune cells of the body's defense against the virus It has been proven that it could be the cause of the destruction of cell nuclei.

He said that this additional treatment, which has proven effective for children under the age of 12 is more effective in the early stages of the injury and gave the example of the situation of children of Suez, where Mahmud told his mother before the emergence of symptoms of the disease after the observed decrease in activity and appetite, and confirmed the death of chickens that were raised, where he received treatment at the beginning of the high temperature and by the involvement of the lungs.
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Background: Studies from the Spanish influenza era reported that transfusion of influenza-convalescent human blood products reduced mortality in patients with influenza complicated by pneumonia. Treatments for H5N1 influenza are unsatisfactory, and convalescent human plasma containing H5N1 antibodies could be an effective therapy during outbreaks and pandemics.
Purpose: To determine whether transfusion with influenza-convalescent human blood products reduced the risk for death in patients with Spanish influenza pneumonia.
Data Sources: Manual search of English-language journals from 1918 to 1925. Citations from retrieved studies were also searched.
Study Selection: Published English-language studies that had at least 10 patients in the treatment group, used convalescent blood products to treat Spanish influenza pneumonia in a hospital setting, and reported on a control or comparison group.
Data Extraction: Two investigators independently extracted data on study characteristics, outcomes, adverse events, and quality.
Data Synthesis: Eight relevant studies involving 1703 patients were found. Treated patients, who were often selected because of more severe illness, were compared with untreated controls with influenza pneumonia in the same hospital or ward. The overall crude case-fatality rate was 16&#37; (54 of 336) among treated patients and 37% (452 of 1219) among controls. The range of absolute risk differences in mortality between the treatment and control groups was 8% to 26% (pooled risk difference, 21% [95% CI, 15% to 27%]). The overall crude case-fatality rate was 19% (28 of 148) among patients who received early treatment (after <4 days of pneumonia complications) and 59% (49 of 83) among patients who received late treatment (after 4 days of pneumonia complications). The range of absolute risk differences in mortality between the early treatment group and the late treatment group was 26% to 50% (pooled risk difference, 41% [CI, 29% to 54%]). Adverse effects included chill reactions and possible exacerbations of symptoms in a few patients.
Limitations: Studies were few and had many methodologic limitations. No study was a blinded, randomized, or placebo-controlled trial. Some pertinent studies may have been missed.

Conclusions: Patients with Spanish influenza pneumonia who received influenza-convalescent human blood products may have experienced a clinically important reduction in the risk for death. Convalescent human H5N1 timely, and widely available treatment that should be studied in clinical trials. plasma could be an effective,

Comment

H5N1 Family Clusters and Limited Human-to-Human Transmission Found in China and Pakistan

By Michelle Cantu, April 11, 2008

On April 8, 2008, the Lancet published results from investigations by Chinese health officials into the 2007 H5N1 influenza family cluster in Jiangsu Province, China. In this cluster, possible human-to-human transmission of the H5N1 virus occurred between two members of a family, who both tested positive for H5N1 virus. The index case, a 24 year old male, is thought to have contracted the virus at a live poultry market; however, the second case (the man’s 52 year old father) had no contact with infected poultry. His only exposure to the virus appears to be through contact with his ill son. According to the article, it cannot be ruled out that the father's exposure to the virus occurred through other means. However, genomic sequencing has shown that both cases were "identical except for one…nucleotide substitution," and that “all [virus] genes were entirely of avian origin.”1

During the investigation, 91 close contacts of one or both cases consented to serological testing and all were negative for H5N1 antibodies. The son died five days following hospitalization and on the same day that H5N1 was confirmed by RT-PCR. According to the Lancet article, the father had provided unprotected bedside care for prolonged periods of time and did not wear personal protective equipment until after the confirmation of H5N1. The father received oseltamivir and later two plasma transfusions from a clinical trial patient that had been vaccinated for H5N1 virus.1

Plasma was obtained 129 days after illness onset from an adult female case and 81 days after illness onset from an adult male case.

Both donors' convalescent plasma tested negative for hepatitis B, hepatitis C, and HIV, and were separated and heat-inactivated at 56°C for 10 h before transfusion.

The male ARDS case received three units (200 mL/unit) of transfused convalescent plasma from the female donor for 2 days, beginning on illness day 13. His H5N1 viral titre in bronchial-alveolar lavage fluid declined substantially and was undetectable for the next 3 consecutive days after receipt of the third convalescent plasma dose.

The female ARDS case, who had a history of bronchiectasis, received one unit (200 mL) of transfused convalescent plasma from the male donor once daily for 3 days, starting on illness day 13.

Further virological testing has not been done for this case. Both cases also received oseltamivir (75 mg po BID) on illness days 10–14 and days 8–12, respectively. Both cases recovered fully and were discharged home.Complications and outcomes

Since this article has no abstract, we have provided an extract of the first 100 words of the full text and any section headings.

To the Editor: A previously healthy 31-year-old male van driver presented to a local clinic in Shenzhen, in southern China, on June 7, 2006, with a 4-day history of a high fever (temperature, 39.9&#176;C), chills, and a cough with clear sputum. A chest radiograph obtained on June 9 revealed large opacities in the lower lobe of the left lung. A reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay and an isolate from a tracheal aspirate were positive for influenza A (H5N1) virus. Treatment with 150 mg of oseltamivir twice daily was started at 2 a.m. on June 12 (Figure 1). After 2 days, . . . [Full Text of this Article]

Jiangsu confirmed the second case of highly pathogenic avian influenza in patients with Human Lu Wei is currently in stable condition. It was revealed that Lu Wei's body temperature has been normal, the lung inflammation also has changed for the better, and can eat normally, the patient's mood is also very stable. Containing avian influenza antibodies in human serum, for the treatment play a key role. \ 【Newspaper reporter on the 10th Nanjing Min electric】

According to informed sources revealed that Lu Wei in late December 3 fever symptoms, throat swelling at the same time, symptoms such as generalized weakness, that is "double pneumonia under" hospital treatment. Diagnosed as being infected with highly pathogenic avian influenza, the Mainland medical treatment for his attention. National Chinese Health Minister Chen Zhu himself as team leader, and lived in Nanjing for this purpose for several days, several cases take part in discussions, listened carefully to the disease analysis and expert advice, and medical experts to discuss the development of treatment programs.

Minister of Health appointed expert, head of

It was revealed that because of pulmonary inflammation, Lu Wei两肺the emergence of large shadow, the experts have focused on him to take the antiviral drug treatment, nutritional support and hormone therapy, infusion every day and constantly adjusted according to disease agents now has been at the gradual improvement of inflammation.

According to the experts involved in treatment, the patient is currently in stable condition and no complications, but in the future will continue to observe the situation. The expert, easily said, "not a big problem."

Vaccine volunteers donate blood to save people

It was revealed that the disease was diagnosed when Lu Wei, his relatives as soon as the Internet has on the body english avian influenza antibodies and blood group matched with his people, they first found a 44-year-old farmer, the farmers are suffering from bird flu after a successful blood transfusion treatment of others, but to do the work anyway, the farmers are reluctant to lose their serum Lu Wei.

Subsequently, there is a laboratory job at the hospital volunteers, he had injected the bird flu vaccines, blood containing anti-bird flu body, he also happened to the blood group B, and Wei Lu of the B blood type match. Therefore, Lu Wei give input in two of the 200 milliliters of serum, a total of 400 milliliters.

Allegedly, this is 400 milliliters contain the avian flu antibodies in serum on the success of Lu Wei treatment has played a pivotal role.

Insiders revealed that the death of the first cases of human highly pathogenic avian influenza陆侃patients, the cause of death is precisely because the absence of timely and correct treatment, because the incidence him, all people have had I thought of the bird flu are just at him only aware of the death fast, but the rescue is late again.

But was seen off at the cremation of the deceased Grandfather

According to relatives said that they go out with a family of four individuals playing the home in recent years are a very rare thing, usually because the U.S. is busy all the time together total less than together.

This family misfortune very saddened by the insiders, it is known, when cremation陆侃all relatives are not allowed to look at the scene (both in medical observation in isolation), only that time had not come into contact with the grandson of a person wearing a Grandfather isolation clothing for him to see them off.

It was also revealed that eating chicken at the same time the mother and girlfriend陆侃blood samples were sent to laboratories in Beijing, the result is negative. Medical experts have said that this may be the two do not belong to her are susceptible due.

Farmer cured of bird flu donates serum for treatment of new human infection

The farmer from East China's Anhui Province, who contracted the deadly H5N1 strain of bird flu last December but was later cured of the avian disease, was called in to donate his serum for treatment of another rural Chinese woman who was confirmed last month to have been infected of the same virus.

Xu Longshan, spokesman and chief of the Fujian Provincial Professional Panel for Prevention and Control of Human Infection of Bird Flu, told Xinhua Saturday health workers from Anhui Province Thursday escorted the farmer, identified by his surname as Li, to Fuzhou, capital of Fujian Province, where experts from the blood center affiliated to the Fujian Provincial Bureau of Health got serum from him the second day.

Li has returned back home.

"The serum was brought to Jian'ou on the same day, and so far, medical workers have carried out the first round of injection on the woman who was just confirmed of being infected of the lethal strain of the avian disease," said Xu.

"The method is new but is for sure to be of some effect in improving the woman's capability of fighting against new rounds of infection," said Xu, who admitted it would take some time before the woman could develop immunity of her own against the avian disease.

Li from Fujian, 44, is a native of Damiao Village, a marketplace in the mountainous township of Xiaosong. The woman, who kept five chickens at her home, developed symptoms including fever on Feb. 18. She had visited village clinics and township hospitals before being hospitalized on Feb. 24 in the Jian'ou City hospital.

She was confirmed to be infected with the virus by the Chinese Center for Disease Control and Prevention on Feb. 27. She is known to have eaten two chickens she had raised, but her husband and son, who also ate the chicken, have not developed bird flu.

According to Xu, the woman patient was found with inflammation on her left lung when she came to the hospital on Feb. 24, but her pneumonia symptoms developed quickly and she went into a coma the next day. A chest X-ray on Feb. 25 shows large shadows on her lungs.

As of Thursday evening, Li's body temperature and pulse had returned to normal, and her lungs and breathing appeared to be functioning better but she was still breathing with the help of a respirator, Xu said.

Doctors say Li is still in a critical condition and they are trying to boost her immunity to prevent further organic infection.

Over ten doctors and medical experts from local hospitals, and Beijing-based Chaoyang Hospital and Ditan Hospital are trying to work out a detailed treatment plan to save Li, said Xu Yongxi, head of the hospital.

Policemen and hospital staff have been seen guarding the ward where the patient is staying and doctors are wearing thick, disinfected suits.

The patient's husband is with her in the hospital, and her 13-year-old son, who now stays in her four-storey house with his grand-mother, looked saddened, and said he hoped his mother could recover soon.

Li from Fujian is the country's first human case of bird flu in seven weeks since China reported on Jan. 10 that the other Li from Anhui, 37, had contracted bird flu last December but had recovered.

The deadly H5N1 strain of bird flu has killed 14 people in China since 2003.

Sep 8, 2006 (CIDRAP News) – A recent report about the use of blood products to treat patients in the Spanish influenza pandemic of 1918 has sparked interest among those concerned about the threat of the next pandemic, but experts say it's far from clear whether the approach would be practicable in a pandemic today.

In a report published last week, US military researchers said blood products obtained from recovering influenza patients apparently helped save the lives of some patients in the 1918 pandemic, and the same approach should be considered today in the face of another pandemic threat.

Combing the medical literature from the Spanish flu era, the researchers found six controlled studies in which the use of blood plasma, serum, or whole blood from recovering flu patients reduced mortality in seriously ill patients. The authors hypothesize that antibodies in the blood products blunted the effects of the flu virus.

"Patients with Spanish influenza pneumonia who received transfusion with influenza-convalescent human blood products may have experienced a clinically important reduction in the risk for death," say Thomas C. Luke, of the Navy Bureau of Medicine and Surgery, and colleagues. Their report was published online by Annals of Internal Medicine.

Luke and colleagues write that borrowed antibodies in blood products have been used to prevent and treat a number of infectious diseases, including rabies, measles, hepatitis B, cytomegalovirus, and respiratory syncytial virus.

Six studies showed benefit
The authors searched eight major medical journals for controlled trials of the use of blood products from recovering flu patients to treat a minimum of 10 severely ill patients. They found eight studies that met their criteria, ranging in size from 43 to 551 patients, with a total of 1,703. None of the trials was blinded or randomized, and the methods were rated as poor by today's standards. Most of the patients were men between the ages of 17 and 45.

Six of the eight studies showed that the treatment improved survival. The overall case-fatality rate for treated patients was 16% (54 of 336), versus 37% among the controls (452 of 1,219). In addition, all eight reports said that patients showed clinical improvement after treatment. Moderate to serious transfusion-related adverse events occurred in 4% (9 of 235) of patients in studies that included such data.

The timing of treatment made a difference. On the basis of data from four studies, patients treated within 4 days of the onset of pneumonia had an overall case-fatality rate of 19% (28 of 148), whereas those treated later had a fatality rate of 59% (49 of 83).

Acknowledged limitations of the analysis include the small size of the studies, the lack of blinding, and the lack of placebo treatment. The authors also say they can't exclude the possibility that other studies yielded negative findings but went unpublished. Therefore they couldn't reach a firm conclusion about the effectiveness of the treatment.

Nonetheless, they recommend that a committee of experts be set up to consider using plasma treatment for H5N1 patients and to recommend a research strategy.

In an editorial accompanying the report, John J. Treanor, MD, an infectious disease expert at the University of Rochester, says the strategy deserves consideration, but he also raises some caveats.

Passive immunotherapy for flu viruses, including H5N1, has worked in lab mice, Treanor writes. Such treatment prevents many viral diseases in humans, but little recent evidence supports using this approach to treat sick patients, he says. Also, obtaining and using blood products for treatment in the midst of an outbreak would involve "formidable logistical hurdles."

Proving the concept of "serotherapy" for H5N1 would require running controlled trials in regions where human H5N1 cases are occurring, Treanor asserts. He believes the effort would be worthwhile: "We can, should, and must explore these issues about serotherapy now, in advance of the pandemic."

Serotherapy called impractical
Other experts who were asked about using this approach in the next pandemic expressed views ranging from guarded interest to dismissive skepticism.

Michael T. Osterholm, PhD, MPH, didn't question the scientific plausibility of the idea, but argued that it wouldn't be practical in a pandemic. Osterholm is director of the University of Minnesota Center for Infectious Disease Research and Policy, publisher of the CIDRAP Web site.

"We won't have the capacity to do much plasmapheresis [harvesting of plasma] of recovered patients because the system—healthcare workers and equipment—will collapse," Osterholm told CIDRAP News. "And with today's safety regulation, you couldn't do it like you did in 1918."

He said supplies and equipment needed for blood transfusions and processing are likely to run out. "The entire healthcare system is a just-in-time delivery system for virtually everything. . . . You couldn't do it if you wanted to, because you just won't have the equipment. Blood banks don't have months and months of inventory on hand. The bags, tubing, needles, and reagents are made offshore."

"Transfusion medicine is going to be severely challenged during a pandemic," Osterholm said. "Just transfusing the blood we need [will be difficult], let alone doing this kind of thing."

Blood-bank official sees logistical problems
Louis Katz, MD, chair of an American Association of Blood Banks task force on pandemic flu and the blood supply, acknowledged that supplies are likely to be a problem but said that using plasma from recovered patients could be helpful in a pandemic.

The idea "is something we're trying to think about, but it hasn't made it into the first edition of our pandemic flu planning guidelines," said Katz, who is executive vice president of the Mississippi Valley Regional Blood Center in Davenport, Iowa.

He said blood banks are likely to run short of both personnel and supplies in a pandemic, but supplies are the bigger worry.

"We take delivery twice a month on critical lab reagents and once or twice a month on pheresis kits, so the maximum [inventory on hand] is a month," Katz said.

His center doesn't have space to store 8 to 12 weeks' worth of supplies, and even if it did, suppliers might not be able to ramp up deliveries to permit stockpiling, he said. "The just-in-time economy has its advantages in terms of efficiency, but in a crunch there are serious problems," he added.

Further, few recovered flu patients would be available to donate plasma in the early stage of a pandemic, Katz said. "I think there are substantial barriers to providing a lot of it during the first wave." He predicted the task would be "substantially easier" in the second wave of a pandemic.

Katz thinks blood banks could get recovered patients to donate plasma, but not until weeks into the pandemic. "I think they'd come in, but whether we could process enough [blood products] to treat meaningful number of patients, I don't know," he said.

If the pandemic resembled those in 1957 and 1968, in which "business operations weren't horribly disrupted, we probably could ramp up and make immune plasma fairly quickly," Katz said. "It totally depends on what happens."

Another question is whether the Food and Drug Administration (FDA) would approve the use of blood plasma to treat flu patients. "It's complicated, but it becomes an issue of labeling," Katz said. "As long as I didn't label it 'hyperimmune influenza plasma,' I think they'd be fairly permissive." Before allowing such a label, the FDA would require clinical trials and other steps to certify the safety, purity, and potency of the product, he said.

Summing up his thoughts on the topic, Katz said, "While theoretically it's a great idea, the logistics are going to be difficult."

Dr. Jed Gorlin, medical director of Memorial Blood Centers in St. Paul, said the concept of using plasma to treat flu patients has been under discussion in blood-bank circles for a while.

Gorlin said blood banks are worried about shortages of blood donors and of staff to collect blood in a pandemic. But he was more optimistic than Katz on the question of supplies and equipment.

The 1918 flu pandemic lasted about 2 months in most places, he said, adding, "For things like bags and so on we easily have a month and often 2 months, so that part we're not particularly concerned about." On the other hand, other supplies, such as N95 breathing masks, may well run out, he said.

"Blood centers are ahead of most hospitals in that we already have lists of critical reagents and equipment," Gorlin said. "We're already sensitive to our supply chain and in some cases we have alternative suppliers."

Transfusion specialist interested
Robert J. Bowman, MD, a transfusion medicine specialist at the University of Minnesota Medical School in Minneapolis, called the proposal "very interesting," at least theoretically.

"I am unsure of the relative success of immunoglobulin preparations in treating viral illness but given the paucity of treatment options the strategy ought to be tried," he commented by e-mail.

Criteria for acceptance of plasma donors would have to be developed, he said. Plasma could be tested for antibodies and used directly, or many units could be pooled and used to make a standardized intravenous immunoglobulin preparation (IVIG), he suggested.

"Not only do I think this is possible, I think the idea should be tried with standardized IVIG preparations," Bowman wrote. If the treatment worked, its applicability would depend on collection agencies having enough staff and enough money to pay for the IVIG, he added.

Bowman predicted that safety and other regulatory issues would be "manageable," but he acknowledged that supply interruptions could be a problem.

He also said he was uncertain how much IVIG would cost or how long it would take to prepare. "We're not talking about days, we're talking weeks or months," he said. "It takes some time to pool it, then you have to fractionate it, and then there's testing. So it's a big deal. But all the technology is there."

Background: Studies from the Spanish influenza era reported that transfusion of influenza-convalescent human blood products reduced mortality in patients with influenza complicated by pneumonia. Treatments for H5N1 influenza are unsatisfactory, and convalescent human plasma containing H5N1 antibodies could be an effective therapy during outbreaks and pandemics.

Purpose: To see whether transfusion with influenza-convalescent human blood products reduced the risk for death in patients with Spanish influenza pneumonia.

Data Sources: Manual search of English-language journals from 1918 to 1925. Citations from retrieved studies were also searched.

Study Selection: Published English-language studies that had at least 10 patients in the treatment group, used convalescent blood products to treat Spanish influenza pneumonia in a hospital setting, and reported on a control or comparison group.

Data Synthesis: Eight relevant studies involving 1703 patients were found. Treated patients, who were often selected because of more severe illness, were compared with untreated controls with influenza pneumonia in the same hospital or ward. The overall crude case-fatality rate was 16% (54 of 336) among treated patients and 37% (452 of 1219) among controls. The range of absolute risk differences in mortality between the treatment and control groups was 8% to 26% (pooled risk difference, 21% [95% CI, 15% to 27%]). The overall crude case-fatality rate was 19% (28 of 148) among patients who received early treatment (after <4 days of pneumonia complications) and 59% (49 of 83) among patients who received late treatment (after ≥4 days of pneumonia complications). The range of absolute risk differences in mortality between the early treatment group and the late treatment group was 26% to 50% (pooled risk difference, 41% [CI, 29% to 54%]). Adverse effects included chill reactions and possible exacerbations of symptoms in a few patients.

Limitations: Studies were few and had many methodologic limitations. No study was a blinded, randomized, or placebo-controlled trial. Some pertinent studies may have been missed.

Conclusions: Patients with Spanish influenza pneumonia who received influenza-convalescent human blood products may have experienced a clinically important reduction in the risk for death. Convalescent human H5N1 plasma could be an effective, timely, and widely available treatment that should be studied in clinical trials.

Comment

The blood stock has to be replaced regularly to keep a current supply of fresh blood and blood products. Blood products are refrigerated and all have a different shelf-life.

* Red blood cells have a shelf life of forty-two days.
* Plateles have a shelf life of five days
* Fresh Frozen Plasma have a shelf life one year.
* Cryoprecipitate have shelf life of one year.
* And Frozen Plasma have a shelf life of four years.

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